Longitudinal change in neurocognition and its relation to symptomatic and functional changes over 2 years in individuals at clinical high-risk for psychosis

https://doi.org/10.1016/j.schres.2016.03.024Get rights and content

Abstract

Background

Negative symptoms and functional disability represent the core of schizophrenia and both are associated with cognitive impairments. We explored the course of cognitive change and its relation to symptomatic and functional changes in individuals at clinical high-risk (CHR) for psychosis to identify cognitive indicators of long-term course. Such attempts may offer insight into the pathological changes associated with the development of illness in the prodromal state.

Methods

Forty-seven CHR individuals completed neurocognitive, clinical, and functional assessments at baseline and 2-year follow-up; twenty-eight healthy controls were assessed for neurocognitive and functional measures at baseline and 2-year follow-up. The delta values of CHR individuals in neurocognitive, clinical, and functional domains were determined from differences between baseline and follow-up scores to estimate the degree of change.

Results

Although overall longitudinal cognitive performance of CHR individuals improved, the magnitude of improvement was not statistically different from that of normal controls at the group level. However, the individual data yielded two groups of CHR subjects showing opposite trajectories of cognitive change in semantic fluency (i.e., improvement or decline), which was significantly associated with changes in negative symptoms and functioning. Moreover, the relationships between negative symptoms and functioning were more strengthened over time than baseline.

Conclusions

Our findings show that semantic fluency seems to be a neurocognitive indicator reflecting clinical courses in CHR individuals. The longitudinal relationship of negative symptoms and functioning with semantic fluency may represent ongoing pathological processes in neural systems involving aberrant fronto–temporal interaction in the early phase of schizophrenia.

Introduction

Understanding the course of cognitive change in individuals at clinical high-risk (CHR) for psychosis may help elucidate the pathological changes that occur early in schizophrenia (Jahshan et al., 2010). However, it should be noted that the considerable heterogeneity of the CHR group may conceal the nature and trajectories of cognitive change associated with the long-term course. Indeed, recent evidence on different types and degree of cognitive impairments at baseline (Fusar-Poli et al., 2013, Giuliano et al., 2012), heterogeneous cognitive and clinical courses (Addington and Barbato, 2012, Lee et al., 2014), and no clear consensus of cognitive factors for conversion to psychosis (Addington and Heinssen, 2012) supports this view. Nevertheless, most longitudinal research of CHR individuals has focused on mean differences in cognitive performance between baseline and follow-up as a group. Such approach, without consideration of individual differences, may represent simplified patterns of long-term cognitive change (Nesselroade, 2002, Roalf et al., 2013). Our goal is to focus on the magnitude of cognitive change in each individual over time.

Furthermore, when the course of cognitive change is in accordance with symptomatic and functional trajectories, the cognitive fluctuation may indicate important changes that are reflective of clinical and functional courses, not just normal performance variability. In schizophrenia, cognitive impairments are most consistently associated with negative symptoms and functional disability (Addington and Addington, 2000, Bilder et al., 2000, Bowie et al., 2006, Brébion et al., 2013, Green et al., 2000, Leeson et al., 2010, Nuechterlein et al., 2011, Shamsi et al., 2011, Ventura et al., 2009). In addition, the relationship between negative symptoms and functioning is well established in chronic (Ventura et al., 2009) and first-episode schizophrenia (Vesterager et al., 2012). In this regard, it is believed that emerging negative symptoms and functional disability in the prodromal phase form the basis on which psychosis develops later (Addington and Heinssen, 2012, Häfner et al., 1999). Recent report on the relationship of neurocognition and negative symptoms to functioning in CHR individuals seems to add more weight to this issue, prompting more specific aspects of the relations (Meyer et al., 2014). Thus, it is becoming clear that assessing the pattern of cognitive change with symptoms and functioning would offer not only a more comprehensive view in better understanding the heterogeneity of CHR, but also insight into the course of illness.

Although a previous work examined the patterns of change in neurocognition, symptoms, and functioning over an 8-month follow-up in CHR and found that the course of cognitive change differentiated CHR individuals with good versus poor functioning (Niendam et al., 2007), this study did not find evidence for a relationship between changes in symptoms and cognitive functioning. Negative symptoms, in particular, are the core feature of schizophrenia (Bleuler, 1950, Foussias and Remington, 2010, Klingberg et al., 2011, Kraepelin, 1919) and are associated with a worse course in CHR (Corcoran et al., 2011). Harvey et al. (2006) have suggested that cognitive and negative symptoms are separable but share similar underlying or related etiology. Given the longitudinal stability of cognitive and negative symptoms over the course of the illness (Harvey et al., 2006), the identification of specific cognitive functioning that is closely linked to changes in negative symptoms in the prodromal state may be important as a window into the pathological process of the illness. Such link may provide a foothold in pursuit of the underlying neurobiology of cognitive changes that take place before the diagnosis of the syndrome. In addition, this study seems to provide limited information on measures of verbal fluency by examining letter fluency alone. Considering relatively severe impairment in semantic fluency in both schizophrenia (Bokat and Goldberg, 2003) and CHR individuals who later convert to psychosis (Becker et al., 2010, Fusar-Poli et al., 2012), the course of semantic fluency with negative symptoms and functioning may offer meaningful information regarding the pathological changes in the prodromal state.

The primary aim of the present study was to explore the course of longitudinal cognitive change and its association with clinical and functional changes over a 2-year follow-up period in CHR individuals. First, we examined how the degree of cognitive change is different between CHR individuals and normal controls over time to observe the overall pattern of cognitive change at the group level. Second, as our main interest, we investigated the association of cognitive change with symptomatic and functional changes in CHR individuals. In particular, we focused on identifying specific cognitive indicators that would represent courses of negative symptoms and functioning. We hypothesized that while CHR subjects as a group may show similar cognitive course to control group, the individual data would display meaningful change in certain cognitive domains that would be significantly related to symptomatic (e.g., negative symptoms) and functional changes in CHR individuals.

Section snippets

Participants

The sample consisted of 47 subjects at CHR for psychosis and 28 healthy controls. The CHR subjects were recruited from the Seoul Youth Clinic (SYC), which is currently conducting a longitudinal study on individuals at high risk for psychosis using criteria from the Comprehensive Assessment of At-Risk Mental States (CAARMS) (Yung et al., 2005) and the Korean version of the Structural Interview for Prodromal Syndrome (SIPS) (Jung et al., 2010, Miller et al., 2003). Among the CHR subjects

Demographic, cognitive, and functional characteristics at baseline

Demographic and clinical characteristics of the study sample are presented in Table 1. No significant group differences in gender or IQ were found. However, the groups did differ in age and education level. As shown in Table 2, CHR subjects displayed poorer performance in semantic fluency (F = 6.482, P = 0.013) and global neurocognitive index (F = 4.928, P = 0.030) than did the healthy controls at baseline. The scores on functional outcomes of the CHR group were significantly lower than those of the

Discussion

To our knowledge, this is the first study to examine the course of cognitive change and its association with symptomatic and functional changes over a 2-year follow-up period in CHR individuals. The longitudinal cognitive performance of CHR individuals showed either improvements or stable patterns, but the magnitude of improvement was not significantly different from that of normal controls in all cognitive domains. Likewise, while the averaging data did not find any meaningful changes of

Role of funding source

This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT and Future Planning (Grant no. 2013R1A2A1A03071089).

Author contributions

Ye Seul Shin was involved in the design, wrote the draft of the manuscript and administered neuropsychological tests to the subjects who participated in this study. So-Yeon Kim helped to analyze the data. Tae Young Lee and Sung Nyun Kim completed a screening interview and clinical scales for the subjects of this study and reviewed the manuscript. Ji-Won Hur and Na Young Shin administered neuropsychological tests to the subjects who participated in this study. Min-Sup Shin assisted with the

Conflict of interest

The authors have declared that there are no financial interests or potential conflicts of interest.

Acknowledgements

None.

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